In this revision to application 1 R01 HL-64141-01 submitted in response to Program Announcement number 98-098, we propose to identify mechanisms explanatory of the strong inverse association between socioeconomic status (SES) over the life course and cardiovascular disease morbidity and mortality, in a bi-ethnic population-based sample of four U.S. communities. Cumulative and contemporaneous effects of diverse SES measures will be tested for their predictive validity on health outcomes, with consideration of differences by gender and ethnicity in their (additive or interactive) effects. Health outcomes will include non-invasively measured subclinical cardiovascular disease, as well as fatal and non-fatal clinical disease manifestations ascertained over the course of 10 years of follow-up. Earlier life course socioeconomic status and measurements of current socioeconomic status and biomedical cardiovascular risk factors will be integrated with geocoded contemporary social environmental exposures to assess their impact on cardiovascular function, metabolic impairments, allostatic load, and subclinical and clinical disease. Multilevel analyses will be performed with the goal of identifying pathways by which socioeconomic status is related to cardiovascular disease, considering relevant health behavior, life styles, psychosocial stressors/support mechanisms, chronic infection/chronic inflammatory burden, autonomic nervous system dysfunction, and sustained metabolic impairments. The potential modification of the above associations by the social environment will be addressed by these analyses, as well as putative differences by gender and ethnicity. These staged analytic goals are made possible by linking Census-based indicators of the social environment to the rich data resources of the Atherosclerosis Risk in Communities (ARIC) Study, a bi-ethnic, community-based sample of men and women aged 45-64 years at the time of their baseline examination in 1987-1989. This cohort was re-examined every three years through January, 1999 with ascertainment of SES during childhood, early adulthood and in mid-life, health-relevant behaviors, numerous measurements of risk factors, and measures of subclinical cardiovascular disease such as carotid artery wall thickness, arterial distensibility, retinopathy, and lower extremity arterial disease. These data, as well as validated information on hospital discharge diagnoses and on cause-specific mortality accrued over 10 years of follow-up will be made available to the study proposed in this application. Additional life course information on the members of the ARIC cohort will be collected during Year 1 of the study. Our goal is to explicate the associations and interactive effects of individual SES attributes and their social context on pathways of development of cardiovascular disease in individuals and populations. Increased insight into the mechanisms responsible for these associations should strengthen the basis for public health preventive measures.